CD20(+) T cells have a predominantly Tc1 effector memory phenotype and are expanded in the ascites of patients with ovarian cancer.

Copyright © 2015 Taylor & Francis Group, LLCRecently, a small subset of T cells that expresses the B cell marker CD20 has been identified in healthy volunteers and in patients with rheumatoid arthritis and multiple sclerosis. The origin of these CD20-positive T cells as well as their relevance in human disease remains unclear. Here, we identified that after functional B cell/T cell interaction CD20 molecules are transferred to the cell surface of T cells by trogocytosis together with the established trogocytosis marker HLA-DR. Further, the presence of CD20 on isolated CD20(+) T cells remained stable for up to 48h of ex vivo culture. These CD20(+) T cells almost exclusively produced IFNγ (∼70% vs. ∼20% in the CD20(-) T cell population) and were predominantly (CD8(+)) effector memory T cells (∼60-70%). This IFNγ producing and effector memory phenotype was also determined for CD20(+) T cells as detected in the peripheral blood and ascitic fluids of ovarian cancer (OC) patients. In the latter, the percentage of CD20(+) T cells was further strongly increased (from ∼6% in peripheral blood to 23% in ascitic fluid). Taken together, the data presented here indicate that CD20 is transferred to T cells upon intimate T cell/B cell interaction. Further, CD20(+) T cells are of memory and IFNγ producing phenotype and are present in increased amounts in ascitic fluid of OC patients.Netherlands Organization for Scientific ResearchDutch Cancer SocietyAlexander von Humboldt Foundatio

Design, synthesis, molecular modelling and in vitro screening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives

Funding: Deanship of Scientific Research at Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia (project # 7101).A new series of N'-substituted benzylidene-2-(4-oxo-2-phenyl-1,4-dihydroquinazolin-3(2H)-yl)acetohydrazide (5a-5h) has been synthesized, characterized by FT-IR, NMR spectroscopy and mass spectrometry and tested against human monoamine oxidase (MAO) A and B. Only (3-methoxy-4-hydroxy)benzoyl substituted compounds gave submicromolar inhibition of MAO-A and MAO-B. Changing the phenyl substituent to methyl on the unsaturated quinazoline ring (12a-12d) decreased inhibition but a less flexible linker (14a-14d) resulted in selective micromolar inhibition of hMAO B providing insight for ongoing design.Publisher PDFPeer reviewe

Vortices in polariton OPO superfluids

This chapter reviews the occurrence of quantised vortices in polariton fluids, primarily when polaritons are driven in the optical parametric oscillator (OPO) regime. We first review the OPO physics, together with both its analytical and numerical modelling, the latter being necessary for the description of finite size systems. Pattern formation is typical in systems driven away from equilibrium. Similarly, we find that uniform OPO solutions can be unstable to the spontaneous formation of quantised vortices. However, metastable vortices can only be injected externally into an otherwise stable symmetric state, and their persistence is due to the OPO superfluid properties. We discuss how the currents charactering an OPO play a crucial role in the occurrence and dynamics of both metastable and spontaneous vortices.Comment: 40 pages, 16 figure

Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC).

<p>Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC)</p

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

Complement factor H contributes to mortality in humans and mice with bacterial meningitis

Background The complement system is a vital component of the inflammatory response occurring during bacterial meningitis. Blocking the complement system was shown to improve the outcome of experimental pneumococcal meningitis. Complement factor H (FH) is a complement regulatory protein inhibiting alternative pathway activation but is also exploited by the pneumococcus to prevent complement activation on its surface conferring serum resistance. Methods In a nationwide prospective cohort study of 1009 episodes with community-acquired bacterial meningitis, we analyzed whether genetic variations in CFH influenced FH cerebrospinal fluid levels and/or disease severity. Subsequently, we analyzed the role of FH in our pneumococcal meningitis mouse model using FH knock-out (Cfh−/−) mice and wild-type (wt) mice. Finally, we tested whether adjuvant treatment with human FH (hFH) improved outcome in a randomized investigator blinded trial in a pneumococcal meningitis mouse model. Results We found the major allele (G) of single nucleotide polymorphism in CFH (rs6677604) to be associated with low FH cerebrospinal fluid concentration and increased mortality. In patients and mice with bacterial meningitis, FH concentrations were elevated during disease and Cfh−/− mice with pneumococcal meningitis had increased mortality compared to wild-type mice due to C3 depletion. Adjuvant treatment of wild-type mice with purified human FH led to complement inhibition but also increased bacterial outgrowth which resulted in similar disease outcomes. Conclusion Low FH levels contribute to mortality in pneumococcal meningitis but adjuvant treatment with FH at a clinically relevant time point is not beneficial

Haemorrhagia post partum; an implementation study on the evidence-based guideline of the Dutch Society of Obstetrics and Gynaecology (NVOG) and the MOET (Managing Obstetric Emergencies and Trauma-course) instructions; the Fluxim study

Contains fulltext : 88435.pdf (publisher's version ) (Open Access)BACKGROUND: One of the most important causes of maternal mortality and severe morbidity worldwide is post partum haemorrhage (PPH). Factors as substandard care are frequently reported in the international literature and there are similar reports in the Netherlands. The incidence of PPH in the Dutch population is 5% containing 10.000 women a year. The introduction of an evidence-based guideline on PPH by the Dutch society of Obstetrics and Gynaecology (NVOG) and the initiation of the MOET course (Managing Obstetrics Emergencies and Trauma) did not lead to a reduction of PPH. This implies the possibility of an incomplete implementation of both the NVOG guideline and MOET-instructions. Therefore, the aim of this study is to develop and test a tailored strategy to implement both the NVOG guideline and MOET-instructions METHODS/DESIGN: One step in the development procedure is to evaluate the implementation of the guideline and MOET-instructions in the current care. Therefore measurement of the actual care will be performed in a representative sample of 20 hospitals. This will be done by prospective observation of the third stage of labour of 320 women with a high risk of PPH using quality indicators extracted from the NVOG guideline and MOET instructions. In the next step barriers and facilitators for guideline adherence will be analyzed by performance of semi structured interviews with 30 professionals and 10 patients, followed by a questionnaire study among all Dutch gynaecologists and midwives to quantify the barriers mentioned. Based on the outcomes, a tailored strategy to implement the NVOG guideline and MOET-instructions will be developed and tested in a feasibility study in 4 hospitals, including effect-, process- and cost evaluation. DISCUSSION: This study will provide insight into current Dutch practice, in particular to what extent the PPH guidelines of the NVOG and the MOET-instructions have been implemented in the actual care, and into the barriers and facilitators regarding guideline adherence. The knowledge of the feasibility study regarding the effects and costs of the tailored strategy and the experiences of the users can be used in countries with a relatively high incidence of PPH. TRIAL REGISTRATION: ClinicTrials.gov NCT00928863

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding